5,5-bis(difluoramino)hexahydro-1,3-dinitropyrimidine (RNFX) and certain electronegatively substituted pyrimidines

ABSTRACT

Calculated performance improvements are expected from a particularly new class of compounds, geminal-bis(difluoramino)-substituted heterocyclic nitramines, when formulated into explosives and propellants. This invention involves novel and nonintuitive methods for the preparation of certain derivatives of 2,2-bis(difluoramino)-N-nitro-1,3-propanediamine which are suitable precursors leading to 5,5-bis(difluoramino)hexahydro-1,3-dinitropyrimidine (RNFX). The invention also involves novel and nonintuitive methods for the preparation of RNFX, a specific member of a general class of compounds with the substructure 2,2-bis(difluoramino)-N-nitro-1,3-propanediamine. RNFX is produced by the use of key intermediates, including tetrahydropyrimidin-5(4H)-ones, which allow formation of the target structural subcomponent, 2,2-bis(difluoramino)-N-nitro-1,3-propanediamine, and a more specific substructure of 2,2-bis(difluoramino)-N,N′-dinitro-1,3-propanediamine. The method of making RNFX, generally, comprises reacting with a difluoramine source, a tetrahydro-1,3-disulfonylpyrimidin-5(4H)-one; reacting with a nitronium source, the resultant 5,5-bis(difluoramino)hexahydro-1,3-disulfonylpyrimidine; N-desulfonation with a nucleophile; cyclization with a formaldehyde equivalent; and recovering said 5,5-bis(difluoramino)hexahydro-1,3-dinitropyrimidine—after “2,2-bis(difluoramino)-N,N′-dinitro-1,3-propanediamine.”In addition, this invention involves 5,5-bis(difluoramino)hexahydropyrimidine derivatives, related geminal-bis(difluoramino)alkylene derivatives, and novel precursors to these new derivatives, by the use of certain novel key intermediates.

STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT

The invention described herein may be manufactured and used by or forthe government of the United States of America for governmental purposeswithout the payment of any royalties thereon or therefor.

MICROFICHE APPENDIX

Not Applicable.

BACKGROUND OF THE INVENTION

1. Field of the Invention

This invention involves the calculated performance improvements expectedfrom a particularly new class of compounds,geminal-bis(difluoramino)-substituted heterocyclic nitramines, whenformulated into explosives and propellants. However,the synthesis ofcertain examples of this class of compounds is difficult andnonintuitive. The certain examples that are particularly syntheticallydifficult are molecules that incorporate thegeminal-bis(difluoramino)alkylene [C(NF₂)₂] component and the nitraminecomponent [N-NO₂] in close proximity, especially when separated by onlya methylene (CH₂) link in order to maintain a low fuel-to-oxidizercomponent ratio and concomitantly high oxygen balance in the productmolecule. This invention involves5,5-bis(difluoramino)hexahydropyrimidine derivatives, relatedgeminal-bis(difluoramino)alkylene derivatives, and novel precursors tothese new derivatives, by the use of certain key intermediates whichallow formation of this target structural subcomponent.

2. Description of the Related Art

The calculated performance improvements expected fromgeminal-bis(difluoramino)-substituted heterocyclic nitramines whenformulated into explosives and propellants has been reported. [Miller,Materials Research Society Proceedings 1996, 418, 3] One example of ahighly desirable structure, described by Miller, is a derivative of5,5-bis(difluoramino)hexahydro-1,3-dinitropyrimidine which has thefollowing formula:

wherein R² is selected from the group consisting of hydrogen, alkyl,such as C₁-C₂ alkyls, and substituted alkyl, such as protectedhydroxymethyl and 1,2-ethanediyl. The highly desirable structure, giventhe acronym RNFX by Miller, exists when R² is hydrogen.

Methodology for preparing a geminal-bis(difluoramino)-substitutednitrogenous heterocycle has been reported by Chapman et al. [Journal ofOrganic Chemistry 1998, 3, 15661], who describe the preparation of3,3,7,7-tetrakis(difluoramino)octahydro-1,5-bis(4-nitrobenzenesulfonyl)-1,5-diazocine;this intermediate has been converted to the corresponding nitramine,3,3,7,7-tetrakis(difluoramino)octahydro-1,5-dinitro-1,5-diazocine, giventhe acronym HNFX [Chapman et al, Journal of Organic Chemistry, 1999, 64,960]. However the preparation of cyclic derivatives of2,2-bis(difluoramino)-N,N′-dinitro-1,3-propanediamine in which thenitramine components are linked with a single-carbon bridge, such asRNFX, has not been previously described.

SUMMARY OF THE INVENTION

This invention involves novel and nonintuitive methods for thepreparation of certain derivatives of2,2-bis(difluoramino)-N-nitro-1,3-propanediamine which are suitableprecursors leading to RNFX. The invention also involves novel andnonintuitive methods for the preparation of RNFX, a specific member of ageneral class of compounds with the substructure2,2-bis(difluoramino)-N-nitro-1,3-propanediamine. RNFX is produced bythe use of key intermediates which allow formation of the targetstructural subcomponents,2,2-bis(difluoramino)-N-nitro-1,3-propanediamine and a more specificsubstructure of 2,2-bis(difluoramino)-N,N′-dinitro-1,3-propanediamine,which has the following structure:

Also, this invention comprises certain unprecedented nitramides andnitramines suitable for conversion to RNFX and a variety of otherdifluoramino-substituted heterocyclic nitramines. An important aspect ofthe present invention the substitution on heterocyclic precursors'nitrogen atoms and intermediate nitramides' nitrogen atoms. The nitrogenatoms of heterocyclic precursors (such as pyrimidines) must be suitablysubstituted, or “protected,” during the process of difluoramination toallow this process to proceed to geminal-bis(difluoramino)alkylenederivatives. Without suitable protection of proximate multiplenitrogens, especially those separated from reacting carbonyl sites by ashort bridge, such as methylene, the process of difluoramination ofketone intermediates does not proceed togeminal-bis(difluoramino)alkylene derivatives. The result ismono(difluoramino)alkylene derivatives or no reaction at all.

An object of this invention is to create a novel explosive andpropellant involving geminal-bis(difluoramino)-substituted heterocyclicnitramines.

Another object of this invention is to create a novel method ofproducing 5,5-bis(difluoramino)hexahydro-1,3-dinitropyrimidine.

BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWING

Not Applicable.

DETAILED DESCRIPTION OF THE INVENTION

The collection of pyrimidine intermediates disclosed in this inventionwhich are suitable for eventual conversion to RNFX must allow formationof a tetrahydropyrimidin-5(4H)-one having the following structure:

wherein Z¹ is selected from the group consisting of halosulfonyl,polyhaloalkanesulfonyl, polyhaloarenesulfonyl, a regioisomer offluoroarenesulfonyl, such as 2-,3- and 4-fluoro-substitutedarenesulfonyl, a regioisomer of cyanoarenesulfonyl, such as 2-,3- and4-cyano-substituted arenesulfonyl polycyanoarenesulfonyl, a regioisomerof nitroarenesulfonyl such as 2-,3- and 4-nitro-substitutedarenesulfonyl, and polynitroarenesulfonyl.

In the invention, a tetrahydropyrimidin-5(4H)-one is a necessaryprecursor to a 5,5-bis(difluoramino)hexahydropyrimidine, based on theknown conversion of ketone carbonyl groups by reaction with difluoramineor difluorosulfamic acid in the presence of a strong acid. Thenitrogen-protecting groups chosen for the new pyrimidine intermediatesand precursors are certain sulfonyl substituents. The particularsulfonyl substituents are chosen from a group that favorably affects thebasicity of the pyrimidine nitrogens to make them less basic than theoxygen sites in the pyrimidine intermediates, in order to allowdifluoramination of the carbonyl oxygens to proceed togeminal-bis(difluoramino)alkylene derivatives.

Suitable intermediates leading to tetrahydropyrimidin-5(4H)-ones includehexahydro-5-pyrimidinols (including their oxygen-protected derivatives)and hexahydro-5-(methylene)pyrimidines. These novel N-sulfonylpyrimidinederivatives include hexahydro-5-pyrimidinols having the structure:

wherein Z¹ is selected from the group consisting of halosulfonyl,polyhaloalkanesulfonyl, a regioisomer of fluoroarenesulfonyl, such as2-,3- and 4-fluoro-substituted arenesulfonyl, polyhaloarenesulfonyl, aregioisomer of cyanoarenesulfonyl, such as 2-,3- and 4-cyano-substitutedarenesulfony polycyanoarenesulfonyl, a regioisomer ofnitroarenesulfonyl, such as 2-,3- and 4-nitro-substituted arenesulfonyland polynitroarenesulfonyl; and

wherein R¹ is selected from the group consisting of hydrogen and analcohol-protecting group.

The novel N-sulfonylpyrimidine derivatives also includehexahydro-5-(methylene)pyrimidines having the following structure:

wherein Z¹ is selected from the group consisting of halosulfonyl,polyhaloalkanesulfonyl, a regioisomer of fluoroarenesulfonyl, such as2-,3- and 4-fluoro-substituted arenesulfonyl, polyhaloarenesulfonyl, aregioisomer of cyanoarenesulfonyl, such as 2-,3- and 4-cyano-substitutedarenesulfonyl polycyanoarenesulfonyl, a regioisomer ofnitroarenesulfonyl, such as 2-,3- and 4-nitro-substituted arenesulfonyland polynitroarenesulfonyl.

In the preferred embodiment, a hexahydro-5-(methylene)pyrimidine isutilized as the intermediate leading to a tetrahydropyrimidin-5(4H)-one.In the present invention, the production ofhexahydro-5-(methylene)pyrimidines is accomplished as follows:

wherein Z¹ is selected from the group consisting of halosulfonyl,polyhaloalkanesulfonyl, polyhaloarenesulfonyl, a regioisomer offluoroarenesulfonyl, such as 2-,3- and 4-fluoro-substitutedarenesulfonyl a regioisomer of cyanoarenesulfonyl, such as 2-,3- and4-cyano-substituted arenesulfonyl polycyanoarenesulfonyl, a regioisomerof nitroarenesulfonyl, such as 2-,3- and 4-nitro-substitutedarenesulfonyl,and polynitroarenesulfonyl.

Hexahydro-5-pyrimidinols and hexahydro-5-(methylene)pyrimidines aresuitable intermediates that can be converted totetrahydropyrimidin-5(4H)-one precursors. For example,hexahydro-5-(methylene)pyrimidines are converted totetrahydropyrimidin-5(4H)-ones by ozonlysis of the exo-methylenesubstituent. Next, these precursors are converted to novel5,5-bis(difluoramino)hexahydropyrimidines and othergeminal-bis(difluoramino)alkylene derivatives by difluoramination.

In the preferred embodiment of the invention, the general path of thereaction, after the formation of a tetrahydropyrimidin-5(4H)-one, isillustrated as follows:

wherein Z¹ is selected from the group consisting of halosulfonyl,polyhaloalkanesulfonyl, polyhaloarenesulfonyl, a regioisomer offluoroarenesulfonyl, such as 2-,3- and 4-fluoro-substitutedarenesulfonyl such as 2-,3- and 4-cyano-substituted arenesulfonyl aregioisomer of cyanoarenesulfonyl, polycyanoarenesulfonyl, a regioisomerof nitroarenesulfonyl, such as 2-,3- and 4-nitro-substitutedarenesulfonyl and polynitroarenesulfonyl; and

wherein R² is selected from the group consisting of hydrogen, alkyl,such as C₁-C₂ alkyls and substituted alkyl, such as protectedhydroxymethy and 1,2-ethanediyl.

In another embodiment of the invention, the reaction may also beaccomplished using a carbonyl, rather than the R² groups illustratedabove. That general path is illustrated as follows:

wherein Z¹ is selected from the group consisting of halosulfonyl,polyhaloalkanesulfonyl, polyhaloarenesulfonyl, a regioisomer offluoroarenesulfonyl, such as 2-,3- and 4-fluoro-substitutedarenesulfonyl a regioisomer of cyanoarenesulfonyl, such as 2-,3- and4-cyano-substituted arenesulfonyl polycyanoarenesulfonyl, a regioisomerof nitroarenesulfonyl, such as 2-,3- and 4-cyano-substitutedarenesulfonyl and polynitroarenesulfonyl.

Tetrahydropyrimidin-5(4,)-ones suitable for conversion to5,5-bis(difluoramino)hexahydropyrimidines are substituted on thenitrogens (positions 1 and 3) by electron-withdrawing sulfonylsubstituents. The particular sulfonyl substituents are chosen from aspecific group that imparts lower basicity to the nitrogens than to theoxygen in the tetrahydropyrimidin-5(4H)-ones. Therefore, thesubstitituent causes the nitrogens to have acid dissociation constants(pK_(a)) of the (protonated) conjugate acid forms of the nitrogen sitesto be less than that of the ketones, typically about −7.

The sulfonyl substituents may include alkanesulfonyl, halosulfonyl, orarenesulfonyl substituents, but the arenesulfonyl must haveelectron-withdrawing subsitituents on the phenyl rings. For example, thenitro group (NO₂) is a suitable electron-withdrawing subsitituent. Anysingle or multiple electron-withdrawing subsitituent(s) thatcollectively lower(s) the basicity of the arenesulfonyl-protectednitrogens below that of the oxygen in correspondingtetrahydropyrimidin-5(4H)-ones is (are) suitable. Similarly,alkanesulfonyl protecting groups may be electronegatively substituted toimpart the same property on the protected nitrogens. In general, thesulfonyl substituent must have an inductive substituent constant (σ_(I)or F) of a value greater than that of unsubstituted benzenesulfonyl,approximately 0.58. Such electronegatively substituted pyrimidines areunprecedented.

The geminal-bis(difluoramino)alkylene derivatives must be susceptible tonitrolysis to form N-protected nitramines (i.e. nitramides) and theintermediate nitramides must be susceptible to deprotection to formdesired nitramine intermediates. Those intermediates then undergocyclization by reaction with aldehydes or other alkylating reagents toform difluoramino-substituted heterocyclic nitramines.

In the final step of the process,2,2-bis(difluoramino)-N,N′-dinitro-1,3-propanediamine intermediate isreacted with an electrophile or alkylating reagent, such as aldehyde,alkylene dihalide, aldehyde equivalent or alkylene di(pseudohalide), toundergo cyclization to a desired difluoramino-substituted heterocyclicnitramine. A cyclic2,2-bis(difluoramino)-N,N′-dinitro-1,3-propanediamine is the same as ageneric 5,5-bis(difluoramino)hexahydro-1,3-dinitropyrimidine when thecyclization is effected by a group containing only a single-carbonlinkage between the two nitrogens (positions 1 and 3). This linkage mayhave additional substituents, but the pyrimidine linkage contains N—C—Natoms directly bonded.

The process of making RNFX consists of nitrolyzing the cyclic2,2-bis(difluoramino)-N,N′-disulfonyl-1,3-propanediamine with nitricacid or other nitronium source to prepare a2,2-bis(difluoramino)-N,N′-dinitro-N,N′-disulfonyl-1,3-propanediamine.This nitrolysis may proceed via a2,2-bis(difluoramino)-N-nitro-1,3-propanediamine intermediate, if achemical linkage bridging the precursor's sulfonamide nitrogens isretained by one of the nitrogens upon nitrolysis. The resulting2,2-bis(difluoramino)-N,N′-dinitro-N,N′-disulfonyl-1,3-propanediamine isthen subjected to nucleophilic displacement of the sulfonyl protectinggroup. In 2,2-bis(difluoramino)propanamine derivatives, thisdeprotection is relatively facile, and appropriate nucleophiles includea wide variety of oxygen, nitrogen and other heteroatom derivatives,examples of which include water, alcohols and amines. The resultingdeprotected nitramine,2,2-bis(difluoramino)-N,N′-dinitro-1,3-propanediamine, is then reactedwith a difunctional electrophile suitable for cyclizing thebisnitramine. A variety of electrophiles are suitable for this purpose,including aldehydes, dihaloalkanes, alkyl pseudohalides, other typicalalkylating reagents, acylating reagents, and sulfonating reagents. Theuse of formaldehyde as the cyclizing reagent produces the simplehexahydropyrimidine product (RNFX).

In the successful examples cited below, 4-nitrobenzenesulfonyl was usedas a role model nitrogen-protecting sulfonyl group to prepareelectronegatively substituted pyrimidines as intermediates andprecursors leading to geminal-bis(difluoramino)alkylene derivatives. Awide variety of other heretofore unknown pyrimidine derivatives suitablefor conversion, successively, to tetrapyrimidin-5-(4H)-ones and then togeminal-bis(difluoramino)alkylene derivatives becomes apparent from areview of known electron-withdrawing properties of sulfonylsubstituents, such as reviewed by Hansch et al., Chemical Reviews 1991,91, 165; these require that inductive substituent constants, σ_(I) or F,are greater than approximately 0.58, the value known for unsubstitutedbenzenesulfonyl. Thus, other suitable electronegatively substitutedpyrimidines include those protected on nitrogen by chlorosulfonyl;fluorosulfonyl; cyanosulfonyl; polyhaloalkanesulfonyls, such asdifluoromethanesulfonyl, trifluoromethanesulfonyl, and allperfluoroalkanesulfonyls; arenesulfonyls appropriately substituted suchthat collective effects of substituents on the arene impart the desiredelectronegativity on the arenesulfonyl, including, but not limited to,nitrobenzenesulfonyl (all isomers) and all polynitrobenzenesulfonyls.

Arenesulfonyl substituents may be based on arenes other than benzene,including various aromatic heterocycles, such as azines. Individualsubstituents on the arenesulfonyl of electronegativity comparable to orgreater than that of nitro impart suitable electronegativity to thesulfonyl subsitituents to make suitable pyrimidine intermediates. Thecollective effect of multiple electronegative substituents ofelectronegativity less than that of nitro would also impart,collectively, the same necessary property of lowered basicity; examplesinclude fluororenesulfonyl polyhaloarenesulfonyl andpolycyanoarenesulfonyl protecting groups; other examples are apparentfrom compilations of quantitative inductive effects, such as Hansch etal. (op. cit.).

In the successful examples cited below, 4-nitrobenzenesulfonyl was usedas a model nitrogen-protecting sulfonyl group to prepare2,2-bis(difluoramino)-N,N′-dinitro-N,N′-bis(4-nitrobenzenesulfonyl)-1,3-propanediamineintermediates susceptible to nucleophilic N-desulfonation and subsequentcyclization by appropriate electrophiles. Based on the known generalsusceptibility of N-alkyl-N-nitrosulfonamides to nucleophilicN-desulfonation, it would be apparent that a variety of other N-sulfonylsubsituents are suitable for the present process of preparing2,2-bis(difluoramino)-N,N′-dinitro-1,3-propanediamine and subsequentcyclized derivatives, including alkanesulfonyl, arenesulfonyl (includingheteroarenesulfonyl), and halosulfonyl protecting groups.

In the successful examples cited below, a cyclic 2,2-bis(difluoramino)-N,N′-disulfonyl-1,3-propanediamine precursor[specifically, 5,5-bis(difluoramino)hexahydro-1,3-bis(4-nitrobenzenesulfonyl)pyrimidine] contained methylene(CH₂) as a bridging link between sulfonamide nitrogens of the reactant;the methylene bridge was susceptible to nitrolysis to an N-nitratomethylsubstituent which was also nitrolyzed, forming an N-nitrosulfonamide.Based on the known susceptibility to nitrolysis of “substitutedmethylene” linkages bridging heterocyclic nitrogens, other5,5-bis(difluoramino)hexahydro-1,3-disulfonylpyrimidines substituted inthe 2-position are also suitable reactants for the nitrolysis stepgenerating 2,2-bis(difluoramino)-N,N′-dinitro-1,3-propanediaminederivatives. The 2-position substituents that remain feasible within thepresent process include a wide variety of alkyl, aryl (includingheteroaryl) and cyclic alkyl (including heterocyclic alkyl)substituents. The class of feasible examples thus includesperhydro-2,2′-bipyrimidines and a variety of other bicyclic systemslinked to the 2-position of the reactant5,5-bis(difluoramino)hexahydro-1,3-disulfonylpyrimidine.

In the successful examples cited below, a formaldehyde equivalentgenerated in situ during nitrolysis of an N-nitratomethyl substituentwas used to recyclize2,2-bis(difluoramino)-N,N′-dinitro-1,3-propanediamine to form RNFX.Based on the known general reactivity of primary nitramines withaldehydes (under acid catalyzed conditions) and other electrophiles, thepresent process is extensible to the formation of other cyclic2,2-bis(difluoramino)-N,N′-dinitro-1,3-propanediamine derivatives viacyclization with alternative electrophiles. For example,1,3-propanediamines are known to condense with glyoxal to formperhydro-2,2′-bipyrimidines;2,2-bis(difluoramino)-N,N′-dinitro-1,3-propanediamine thus forms5,5,5′,5′-tetrakis(difluoramino)perhydro-1,1′,3,3′-tetranitro-2,2′-bipyrimidinewith glyoxal.

Although the description above contains many specificities, these shouldnot be construed as limiting the scope of the invention but as merelyproviding an illustration of the presently preferred embodiment of theinvention. Thus the scope of this invention should be determined by theappended claims and their legal equivalents.

EXAMPLES Example 1

Preparation of hexahydro-1,3-bis(4-nitrobenzenesulfonyl)-5-pyrimidinol

A 37% aqueous solution of formaldehyde (1.34 mL) was added dropwise to astirred solution of 1,3-diamino-2-hydroxypropane (Aldrich Chemical Co.,95% purity, 1.5 g, 17 mmol) in 8 mL of water over 30 minutes at roomtemperature. After stirring at room temperature for 3 days, the solventwas removed via distillation to give a light yellow solid,hexahydro-5-pyrimidinol.

A solution of hexahydro-5-pyrimidinol (1.0 g, 9.8 mmol) and sodiumcarbonate (1.04 g, 9.8 mmol) in 10 mL of water in a 250 mL round bottomflask was stirred with a magnetic stir bar for 10 minutes. A solution of4-nitrobenzenesulfonyl chloride (4.4 g, 19.8 mmol) in 10 mL of toluenewas added dropwise over a period of 30 minutes. The reaction mixtureformed a white suspended solid. A mixture of 100 mL of water and 20 mLof toluene was added to the reaction mixture and stirred overnight. Thereaction mixture was filtered and the solid was washed with 100 mL oftoluene, then with 100 mL of water. The solid was dried at roomtemperature under reduced pressure to give 4.4 g (95%) of crude product,hexahydro-1,3-bis(4-nitrobenzenesulfonyl)-5-pyrimidinol. [¹H NMR(DMSO-d₆): δ 2.29 (s, 1 H), 2.84, 3.47 {AB q of d, J=12.4(3.8) Hz,12.4(7.9) Hz, 4 H}, 3.30 (m, 1 H), 4.46, 5.07 (AB q, J=12.5 Hz, 2 H),5.31 (s, 1 H), 8.11, 8.41 (AB q, J=8.7 Hz, 8 H); ¹³C NMR (DMSO-d₆): δ50.0, 59.8, 60.6, 124.6, 128.9, 143.3, 150.1].

Example 2

Preparation ofhexahydro-5-(methylene)-1,3-bis(4-nitrobenzenesulfonyl)pyrimidine

A suspended mixture of 4-nitrobenzenesulfonamide (2.0 g, 9.9 mmol) andpotassium carbonate (0.68 g, 4.9 mmol) in 100 mL water was stirred andheated at 70° C. until the reaction mixture turned clear. Aqueous 37%formaldehyde (0.2 mL, 4.9 mmol) was added and the mixture heated at 70°C. for 3 days. The reaction mixture was concentrated by removal of watervia rotary evaporation at reduced pressure. The reaction mixture wasneutralized to pH 7 with hydrochloric acid. The resulting solid wasfiltered and washed with water to give 0.7 g (18%) ofmethylenebis(4-nitrobenzenesulfonamide) [¹H NMR (acetone-d₆): δ 2.82 (s,2 H), 4.86 (m, 2 H), 8.07, 8.35 (AB q, J=8.9 Hz, 8 H); ¹³C NMR(acetone-d₆) δ 53.0, 125.2, 129.1, 148.4, 151.0]. The yield of thisreaction ranged from 10-30%. A mixture ofmethylenebis(4-nitrobenzenesulfonamide) (1.0 g, 2.4 mmol), potassiumcarbonate (0.66 g, 4.8 mmol), and 3-chloro-2-(chloromethyl)-1-propene(0.3 g, 2.4 mmol) in 150 mL of acetonitrile was stirred and heated atreflux under a nitrogen atmosphere for 20 h. The solvent was removedunder reduced pressure, and the remaining solid was chromatographed(silica gel-ethyl acetate) to give 0.84 g (75%) of solid,hexahydro-5-(methylene)-1,3-bis(4-nitrobenzenesulfonyl)pyrimidine [¹HNMR (acetone-d₆): δ 3.90 (s, 4 H), 4.95 (m, 2 H), 5.00 (s, 2 H), 8.18,8.44 (AB q of t, J=9.0(2.2) Hz, 8 H); ¹³C NMR (acetone-d6): δ 51.0,61.7, 116.2, 125.3, 130.6, 133.6, 144.6, 151.6].

Example 3

Preparation oftetrahydro-1,3-bis(4-nitrobenzenesulfonyl)pyrimidin-5(4H)-one

A stream of ozone in oxygen was bubbled into a solution ofhexahydro-5-(methylene)-1,3-bis(4-nitrobenzenesulfonyl)pyrimidine (0.6g, 1.3 mmol) in 150 mL acetone at −78° C. (dry ice-acetone bath) until ablue color persisted for 5 minutes. The reaction was stirred for 15minutes under a nitrogen atmosphere. Next, 2.0 mL of dimethyl sulfidewas added. After stirring for 10 minutes, the solvent was removed andthe solid dried under reduced pressure to give 0.5 g (83%) oftetrahydro-1,3-bis(4-nitrobenzenesulfonyl)pyrimidin-5(4H)-one. [¹H NMR(acetone-d₆): δ 3.95 (s, 4 H), 5.25 (s, 2 H), 8.20, 8.48 (AB q, J=9.0Hz, 8 H); ¹³C NMR (DMSO-d₆): δ 53.8, 58.8, 124.8, 129.3, 141.9, 150.4,196.2].

Example 4

Preparation of2,2-bis(difluoramino)-N,N′-bis(difluoraminomethyl)-N,N′-(4-nitrobenzenesulfonyl)-1,3-propanediamine

Difluoramine (2.2 g, 41.5 mmol) was absorbed into a mixture of 3.0 mLfuming sulfuric acid (30% SO₃) plus 100 mL of trichlorofluoromethane ina temperature range of −15 to +5° C.Tetrahydro-1,3-bis(4-nitrobenzenesulfonyl)pyrimidin-5(4H)-one (0.255 g,0.54 mmol) was added via a solid addition funnel with another 15 mL oftrichlorofluoromethane to wash out the funnel. After 3 h stirring at−15° C., the reaction mixture was poured onto ice. The mixture wasbasified with aqueous sodium carbonate to pH 6 and then extracted withdichloromethane. The solvent was removed from this extract by rotaryevaporation and the residue was redissolved in chloroform andchromatographed on silica gel, eluting successively with chloroform (twofractions) and dichloromethane (three fractions). Fraction #2, eluted bychloroform, contained a mixture of2,2-bis(difluoramino)-N,N′-bis(difluoraminomethyl)-N,N′-(4-nitrobenzenesulfonyl)-1,3-propanediamine[¹H NMR (chloroform-d): δ 4.39 (s), 5.09 (t), 8.12, 8.44 (AB q, J=8.9Hz); ¹⁹F NMR (chloroform-d): δ 30.59 (s), 44.86 (t, J=22.9 Hz)] andN,N-bis(difluoraminomethyl)-4-nitrobenzenesulfonamide [¹H NMR(chloroform-d): δ 5.03 (t, J=22.6 Hz, 4 H), 8.09, 8.42 (AB q, J=8.9 Hz,8 H); ¹⁹F NMR (chloroform-d): δ 43.53 (t, J=22.4 Hz)].

Example 5

Preparation of5,5-bis(difluoramino)hexahydro-1,3-bis(4-nitrobenzenesulfonyl)pyrimidineand5,5-bis(difluoramino)-1-(difluoraminomethyl)hexahydro-3-(4-nitrobenzenesulfonyl)pyrimidine

The same reaction as described in Example 4 is performed. Elution ofchromatography Fraction #3 with dichloromethane produced a mixturecontaining predominantly5,5-bis(difluoramino)hexahydro-1,3-bis(4-nitrobenzenesulfonyl)pyrimidine[¹H NMR (dichloromethane-d₂-chloroform-d): δ 3.98 (s, 4 H), 4.98 (s, 2H), 8.07, 8.42 (AB q, J=9.0 Hz, 8 H); ¹³C NMR(dichloromethane-d₂-chloroform-d): δ 44.3 (m, J=9.0 Hz), 60.4, 89.7 (m),125.3, 129.5, 144.0, 151.4; ¹⁹F NMR (dichloromethane-d₂-chloroform-d): δ27.27] plus minor amounts of5,5-bis(difluoramino)-1-(difluoraminomethyl)hexahydro-3-(4-nitrobenzenesulfonyl)pyrimidine [¹⁹F NMR (dichloromethane-d₂-chloroform-d): δ 21.65,28.15 (AB q, J=610 Hz, 4 F), 45.38 (t, J=20.8 Hz, 2 F)],N-(difluoraminomethyl)-4-nitrobenzenesulfonamide [¹⁹F NMR(dichloromethane-d₂-chloroform-d): δ 39.86 (td, J=22.6, 7.6 Hz)] andN,N-bis(difluoraminomethyl)-4-nitrobenzenesulfonamide.

Example 6

Preparation of5,5-bis(difluoramino)hexahydro-1,3-bis(4-nitrobenzenesulfonyl)pyrimidine

The same reaction as in Example 4 is performed. Elution ofchromatography Fraction #4 with dichloromethane produced effectivelypure 5,5-bis(difluoramino)hexahydro-1,3-bis(4-nitrobenzenesulfonyl)pyrimidine.

Example 7

Preparation of2,2-bis(difluoramino)-N-(nitratomethyl)-N-nitro-N,N′-bis(4-nitrobenzenesulfonyl)-1,3-propanediamine

5,5-Bis(difluoramino)hexahydro-1,3-bis(4-nitrobenzenesulfonyl)pyrimidineis dissolved in a large excess of ca. 98% nitric acid. Nitrolysis of themethylene bridge in this reactant is conveniently followed by ¹⁹F NMRspectrometry. Nitrolysis initially produces2,2-bis(difluoramino)-N-(nitratomethyl)-N′-nitro-N,N′-bis(4-nitrobenzenesulfonyl)-1,3-propanediamine[¹H NMR (HNO₃): δ 4.53 (s), 5.09 (s), 5.88 (s), 8.42, 8.78 (AB q, J=9.0Hz, 4 H, N-aryl), 8.43, 8.70 (AB q, J=9.0 Hz, 4 H, N′-aryl); ¹³C NMR(HNO₃): δ 44.2, 45.8, 60.6, 90.8, 125.6, 128.6, 131.3, 143.1, 146.6,150.5, 151.6; ¹⁹F NMR (HNO₃): δ 29.39].

Example 8

Preparation of 2,2-bis(difluoramino)-N,N′-dinitro-1,3-propanediamine

Nitrolysis of the intermediate formed in Example 7 replaces theN-nitratomethyl substitituent with N-nitro. The reaction rates of thesuccessive nitrolysis steps are expectedly influenced by theconcentration of reactants—the sulfonamides and nitric acid. With aproper proportion of reactants, the next step of the sequence occursspontaneously:2,2-bis(difluoramino)-N,N′-dinitro-N,N′-bis(4-nitrobenzenesulfonyl)-1,3-propanediamineis adventitiously N-desulfonated by the water contained in theconcentrated nitric acid, forming2,2-bis(difluoramino)-N,N′-dinitro-1,3-propanediamine, which does notaccumulate but combines spontaneously with the formaldehyde equivalentgenerated in this nitrolysis, as described in Example 9.

Example 9

Preparation of 5,5-bis(difluoramino)hexahydro-1,3-dinitropyrimidine(RNFX)

Under the conditions of nitrolysis of2,2-bis(difluoramino)-N-(nitratomethyl)-N-nitro-N,N′-bis(4-nitrobenzenesulfonyl)-1,3-propanediaminein ca. 98% nitric acid, the liberated formaldehyde equivalent becomesavailable for cyclization of the N-desulfonated bis(primary nitramine),2,2-bis(difluoramino)-N,N′-dinitro-1,3-propanediamine. The cyclizationoccurred spontaneously at room temperature, consuming the2,2-bis(difluoramino)-N,N′-dinitro-1,3-propanediamine intermediate andforming 5,5-bis(difluoramino)hexahydro-1,3-dinitropyrimidine (RNFX) [¹HNMR (CD₃CN): δ 4.85 (s, 4 H), 6.06 (s, 2 H); ¹H NMR (acetone-d₆): δ 5.07(s, 4 H), 6.31 (s, 2 H); ¹³C NMR (CD₃CN): δ 45.3 (m, J=6 Hz), 60.6 (s)(not all carbons detected due to low S/N); ¹⁹F NMR (CD₃CN): δ 29.67; ¹⁹FNMR (acetone-d₆): δ 29.31)].

What is claimed is:
 1. A5,5-bis(difluoramino)hexahydro-1,3-dinitropyrimidine having a formulaselected from the group consisting of:

wherein R² is selected from the group consisting of hydrogen, C₁-C₂alkyl, protected hydroxymethyl and 1,2 ethanediyl.
 2. A method ofpreparing a 5,5-bis(difluoramino)hexahydro-1,3-dinitropyrimidine whichcomprises the steps of: reacting with a difluoramine source atetrahydro-1,3-disulfonylpyrimidin-5(4H)-one; reacting, with a nitroniumsource, a resultant5,5-bis(difluoramino)hexahydro-1,3-disulfonylpyrimidine having a formulaselected from the group consisting of:

N-desulfonation with a nucleophile; cyclization with a formaldehydeequivalent; and recovering said5,5-bis(difluoramino)hexahydro-1,3-dinitropyrimidine; wherein R² isselected from the group consisting of hydrogen, C₁-C₂ alkyl, protectedhydroxymethyl and 1,2 ethanediyl; and wherein Z¹ is a sulfonylsubstituent selected from the group consisting of halosulfonyl,polyhaloalkanesulfonyl, a regioisomer of fluoroarenesulfonyl,polyhaloarenesulfonyl, a regioisomer of cyanoarenesulfonyl,polycyanoarenesulfonyl, a regioisomer of nitroarenesulfonyl, andpolynitroarenesulfonyl.
 3. The method according to claim 2 wherein saidnitronium source is selected from the group consisting of nitric acid, anitronium salt, and a covalent nitryl derivative.
 4. The methodaccording to claim 2, wherein said reacting with a nitronium sourcetakes place at a temperature ranging from about −80° C. to about 120° C.5. A pyrimidinol having a formula selected from the group consisting of:

wherein R¹ is selected from the group consisting of hydrogen and analcohol protecting group; wherein R² is selected from the groupconsisting of hydrogen, C₁-C₂ alkyl, protected hydroxymethyl and1,2ethanediyl; and wherein Z¹ is a sulfonyl substituent selected fromthe group consisting of halosulfonyl, polyhaloalkanesulfonyl, aregioisomer of fluoroarenesulfonyl, polyhaloarenesulfonyl, a regioisomerof cyanoarenesulfonyl, polycyanoarenesulfonyl, a regioisomer ofnitroarensulfonyl, and polynitroarenesulfonyl.
 6. A pyrimidine having aformula selected from the group consisting of:

wherein R² is selected from the group consisting of hydrogen, C₁-C₂alkyl, protected hydroxymethyl and 1,2ethanediyl; and wherein Z¹ is asulfonyl substituent selected from the group consisting of halosulfonyl,polyhaloalkanesulfonyl, a regioisomer of fluoroarenesulfonyl,polyhaloarenesulfonyl, a regioisomer of cyanoarenesulfonyl,polycyanoarenesulfonyl, a regioisomer of nitroarensulfonyl, andpolynitroarenesulfonyl.
 7. A tetrahydropyrimidin-5(4H)-one having aformula selected from the group consisting of:

wherein R² is selected from the group consisting of hydrogen, C₁-C₂alkyl, protected hydroxymethyl and 1,2ethanediyl; and wherein Z¹ is asulfonyl substituent selected from the group consisting of halosulfonyl,polyhaloalkanesulfonyl, a regioisomer of fluoroarenesulfonyl,polyhaloarenesulfonyl, a regioisomer of cyanoarenesulfonyl,polycyanoarenesulfonyl, a regioisomer of nitroarensulfonyl, andpolynitroarenesulfonyl.
 8. The process of claim 2 wherein said sulfonylsubstituent has an inductive substituent constant greater than 0.58. 9.The pyrimidinol of claim 5 wherein said sulfonyl has an inductivesubstituent constant greater than 0.58.
 10. The pyrimidinol of claim 6wherein said sulfonyl has an inductive substituent constant greater than0.58.
 11. The tetrahydropyrimidin-5(4H)-one of claim 7 wherein saidsulfonyl substituent constant greater than 0.58.
 12. The process ofclaim 2 wherein said regioisomer of fluoroarenesulfonyl is selected fromthe group consisting of 2-,3- and 4-fluoro-substituted arensulfonyl,wherein said regioisomer of cyanoarenesulfonyl is selected from thegroup consisting of 2-,3- and 4-fluoro-substituted arensulfonyl andwherein said regioisomer of nitroarenesulfonyl is selected from thegroup consisting 2-,3- and 4-nitro-substituted arensufonyl.
 13. Thepyrimidinol of claim 5 wherein said regioisomer of fluoroarenesulfonylis selected from the group consisting of 2-,3- and 4-fluoro-substitutedarensufonyl, wherein said regioisomer of cyanoarenesulfonyl is selectedfrom the group consisting of 2-,3- and 4-cyano-substituted arensufonyland wherein said regioisomer of nitroarenesulfonyl is selected from thegroup consisting 2-,3- and 4-nitro-substituted arensufonyl.
 14. Thepyrimidinol of claim 6 wherein said regioisomer of fluoroarenesulfonylis selected from the group consisting of 2-,3- and 4-fluoro-substitutedarensufonyl, wherein said regioisomer of cyanoarenesulfonyl is selectedfrom the group consisting of 2-,3- and 4-cyano-substituted arensufonyland wherein said regioisomer of nitroarenesulfonyl is selected from thegroup consisting 2-,3- and 4-nitro-substituted arensufonyl.
 15. Thetetrahydropyrimidin-5(4H)-one of claim 7 wherein said regioisomer offluoroarenesulfonyl is selected from the group consisting of 2-,3- and4-fluoro-substituted arensufonyl, wherein said regioisomer ofcyanoarenesulfonyl is selected from the group consisting of 2-,3- and4-cyano-substituted arensufonyl and wherein said regioisomer ofnitroarenesulfonyl is selected from the group consisting 2-,3- and4-nitro-substituted arensufonyl.